Jean-luc Six - Academia.edu (original) (raw)
Papers by Jean-luc Six
HAL (Le Centre pour la Communication Scientifique Directe), Jan 16, 2014
Polymer, 2002
The silylation reaction of dextran with 1,1,1,3,3,3-hexamethyldisilazane (HMDS) in DMSO was studi... more The silylation reaction of dextran with 1,1,1,3,3,3-hexamethyldisilazane (HMDS) in DMSO was studied as the ®rst step of the synthesis of new amphiphilic polyester-grafted dextrans. According to the experimental conditions, i.e. dextran molar weight, medium temperature and reaction time, HMDS/OH ratio, addition of a catalyst and co-solvent, partially or totally silylated dextrans were recovered. The highest silylation yields were obtained with the lowest molecular weight dextrans. The increase in temperature medium and/or reaction time, the presence of catalyst or co-solvent favored the protection yield. Whatever the dextran used, complete silylation of the polysaccharide chain could be achieved by adequate selection of the experimental conditions. The thermal properties of resulting silylated polysaccharides were investigated by temperature modulated DSC. It was observed that T g values of partially silylated dextran were maintained between 120 and 140 8C, independently of the dextran molecular weight. Interestingly, DMSO proved to behave as an ef®cient plasticizer of (partially) silylated dextrans. The partially silylated dextrans were ef®ciently used as multifunctional macroinitiators for the controlled ring-opening polymerization (ROP) of lactone. The ROP was then promoted from the remaining hydroxyl groups in the presence of tin or aluminium activator. After polymerization and ultimate deprotection of the silylated dextran backbone, amphiphilic polyester-grafted dextrans were readily recovered. q (J.-Luc Six). Fig. 1. Dextran structure. Scheme 1. Strategy of poly(1-caprolactone)-grafted dextran synthesis.
Bio-medical materials and engineering, 2010
The aim of this study is to evaluate the toxicity of nanoparticles of poly(D,L-lactic acid) (PLA)... more The aim of this study is to evaluate the toxicity of nanoparticles of poly(D,L-lactic acid) (PLA) or poly(D,L-lactic-co-glycolic acid) (PLGA) covered by chemically esterified amphiphilic hyaluronate (HA) which will be used for intra-articular injection as a drug carrier for the treatment of arthritis (RA) and/or osteoarthritis (OA). PLA and PLGA are FDA approved polymers that are already used for the preparation of nano or microparticles. HA is a natural polysaccharide already present in the articulations known to interact with the CD44 receptors of the cells (especially chondrocytes). Therefore, we can envisage that the HA covering can improve the interactions between the cells and the nanoparticles, leading to better targeting or biodistribution. The knee of healthy male rats was injected one to two times weekly, with various concentrations of nanoparticles encapsulating Dextran-FITC. The synovial membranes and the patellae were collected aseptically and histologically analyzed to...
Macromolecules, 2000
ABSTRACT The combination of bioresorbable and biodegradable hydrophilic polysaccharides with biod... more ABSTRACT The combination of bioresorbable and biodegradable hydrophilic polysaccharides with biodegradable hydrophobic polyester chains to form totally biodegradable, nonionic brushlike amphiphilic graft copolymers useful as surfactants has been investigated. In fact, a totally controlled and original three-step procedure is described which gives access to a wide range of poly(ε-caprolactone)-grafted dextran copolymer compositions. It consists of the reversible protection of the hydroxyl groups of the polysaccharide backbone by silylation, followed by the ring-opening polymerization of ε-caprolactone initiated by the free remaining hydroxyl groups of the partially silylated dextran in the presence of aluminum and tin-based catalysts. The last step relies upon the removal of silylating groups under mild acidic conditions yielding the desired amphiphilic graft copolymers.
Macromolecules, 2004
ABSTRACT A large variety of amphiphilic polylactide-grafted dextrans has been synthesized with co... more ABSTRACT A large variety of amphiphilic polylactide-grafted dextrans has been synthesized with controlled architecture through a three-step procedure: partial protection of the dextran hydroxyl groups by silylation; ring-opening polymerization of D,L-lactide initiated from remaining hydroxyl groups on partially silylated dextran; and silyl ether deprotection under very mild conditions. Throughout the synthesis, detailed characterizations of each step led to the control of copolymer architecture in terms of graft number and lengths of graft and backbone. Depending on their proportion in polylactide, these copolymers were either water-soluble or soluble in organic solvents. The potential of these amphiphilic grafted copolymers as surfactants was estimated. Their organization at air/water or dichloromethane/water interfaces was investigated by interfacial tension measurements. Self-organization in water or toluene was evaluated using fluorescence spectroscopy. Depending on its solubility, each copolymer showed noticeable surfactant properties and was able to produce either hydrophobic or hydrated microdomains in water or toluene solutions, respectively.
Journal of Polymer Science Part A: Polymer Chemistry, 2008
The four-step synthesis of amphiphilic glycopolymers associating dextran as backbone and poly(met... more The four-step synthesis of amphiphilic glycopolymers associating dextran as backbone and poly(methyl methacrylate) (PMMA) as grafts is reported, using the ''grafting from'' strategy. In the first step, the dextran OH functions were partially acetylated. The second step consisted in linking initiator groups by reaction of 2-bromoisobutyryl bromide (B i BB) with the unprotected OH functions. Third, the atom transfer radical polymerization (ATRP) of methyl methacrylate was carried out in DMSO from the resulting dextran derivative used as a macroinitiator. Finally, the cleavage of the acetate groups led to the expected glycopolymers. Careful attention was given both to the copolymer structure and the control of polymerization. PMMA grafts were analyzed by SEC-MALLS after their deliberate cleavage from the backbone to evidence a controlled polymerization. Moreover, the mildness of the final deprotection conditions was proved to ensure acetate cleavage without either degrading dextran backbone and PMMA grafts or cleaving grafts from dextran backbone.
Journal of Polymer Science Part A: Polymer Chemistry, 2011
The synthesis of amphiphilic dextran-g-poly(methyl methacrylate) glycopolymers (Dex-g-PMMA) is st... more The synthesis of amphiphilic dextran-g-poly(methyl methacrylate) glycopolymers (Dex-g-PMMA) is studied using ''grafting from'' concept and atom transfer radical polymerization. Two strategies have been examined to control the macromolecular parameters of such glycopolymers. One is involving four steps including a protection/deprotection approach and the second one only two steps. The introduction of initiators group onto a protected acetylated dextran (and directly onto dextran) was achieved resulting in protected DexAcBr (and in unprotected DexBr). These two types of polysaccharidic macroinitiators differ in term of solubility (hydrophilic DexBr vs.
Journal of Polymer Science Part A: Polymer Chemistry, 2004
The whole controlled synthesis of novel amphiphilic polylactide (PLA)grafted dextran copolymers w... more The whole controlled synthesis of novel amphiphilic polylactide (PLA)grafted dextran copolymers was achieved. The control of the architecture of such biodegradable and potentially biocompatible copolymers has required a three-step synthesis based on the "grafting from" concept. The first step consisted of the partial silylation of the dextran hydroxyl groups. This protection step was followed by the ring-opening polymerization of D,L-lactide initiated from the remaining OH functions of the partially silylated polysaccharide. The third step involved the silylether group deprotection under very mild conditions. Based on previous studies, in which the control of the first step was achieved, this study is focused on the last two steps. Experimental conditions were investigated to ensure a controlled polymerization of D,L-lactide, in terms of grafting efficiency, graft length, and transesterification limitation. After polymerization, the final step was studied in order to avoid degradation of both polysaccharide backbone and polyester grafts. The chemical stability of dextran backbone was checked throughout each step of the synthesis. PLA-grafted dextrans and PLA-grafted (silylated dextrans) were proved to adopt a core-shell conformation in various solvents. Furthermore, preliminary experiments on the potential use of these amphiphilic grafted copolymers as liquid/liquid interface stabilizers were performed.
Journal of Polymer Science Part A: Polymer Chemistry, 2013
A cholesterol-based liquid crystal monomer, diethylene glycol cholesteryl ether acrylate (DEGChol... more A cholesterol-based liquid crystal monomer, diethylene glycol cholesteryl ether acrylate (DEGCholA), has been successfully polymerized by atom transfer radical polymerization (ATRP) for the first time. Appropriate experimental conditions to control the polymerization of DEGCholA have been investigated using a model initiator (ethyl 2-bromoisobutyrate) in tetrahydrofuran (THF) or toluene at 60 C. Well-controlled ATRP of DEGCholA was obtained using N,N,N 0 ,N 0 ,N 00 -pentamethyldiethylenetriamine as ligand in THF at 60 C. These conditions were then applied to initiate the ATRP of DEGCholA from multifunctional macroinitiators based on dextran. Using a protection/ deprotection synthetic scheme, novel graft glycopolymers (Dex-g-PDEGCholA) have been synthesized. The mesomorphic properties of DEGCholA, PDEGCholA, and Dex-g-PDEGCholA have been studied by thermal polarizing optical microscopy, differential scanning calorimetry, and X-ray scattering. PDEGCholA and Dex-g-PDEGCholA show an interdigitated smectic A phase (SmA d ) between T g (30 C) and around 170 C.
Journal of Polymer Science Part A: Polymer Chemistry, 2014
ABSTRACT Poly(d,l-lactide-co-glycolide) (PLGA) copolyesters are commonly used in biomedical appli... more ABSTRACT Poly(d,l-lactide-co-glycolide) (PLGA) copolyesters are commonly used in biomedical applications. Researches were carried out on nontoxic or low-toxic catalysts that are enough efficient to provide short polymerization times, adequate microstructure chains and similar properties than the commercial PLGA materials. In this study, PLGA were synthesized by ring-opening copolymerization (ROP) using three different catalysts. Stannous octoate is the first catalyst we used, as it is very efficient, even its toxicity is still on debate. Two others low-toxic catalysts [zinc lactate and bismuth subsalicylate (BiSS)] were also evaluated. The comparison of these ROP was realized in terms of kinetics and control of the polymerization. Then, the influence of the catalyst on the PLGA microstructure chains is reported. Finally, abiotic hydrolytic degradation rate is studied. Results described in this article show that BiSS is one very attractive catalyst to produce low toxic PLGA for biomedical applications. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014
Journal of Colloid and Interface Science, 2009
Polysaccharide-covered polyester nanoparticles were prepared using the emulsion/solvent evaporati... more Polysaccharide-covered polyester nanoparticles were prepared using the emulsion/solvent evaporation process. The core of the nanoparticles was made either of PLA or of a blend of polylactide and polylactide-grafted dextran copolymer in various proportions. The surface of the nanoparticles was covered by dextran chains via the use of water-soluble polylactide-grafted dextrans as polymeric stabilizers during the emulsification step. The characteristics of the nanoparticles (size, surface coverage, thickness of superficial layer, colloidal stability) were correlated to the structural parameters (length and number of polylactide grafts) of the copolymers as well as to their surface active properties. The complete biodegradability of the nanoparticles was evaluated by considering the rate of hydrolysis of polylactide grafts in phosphate buffer and the rate of enzymatic degradation of dextran backbone by dextranase.
Journal of Biomedical Materials Research Part A, 2000
We developed a novel technique involving knitting and electrospinning to fabricate a composite sc... more We developed a novel technique involving knitting and electrospinning to fabricate a composite scaffold for ligament tissue engineering. Knitted structures were coated with poly(L-lactic-co-e-caprolactone) (PLCL) and then placed onto a rotating cylinder and a PLCL solution was electrospun onto the structure. Highly aligned 2-lm-diameter microfibers covered the space between the stitches and adhered to the knitted scaffolds. The stress-strain tensile curves exhibited an initial toe region similar to the tensile behavior of ligaments. Composite scaffolds had an elastic modulus (150 6 14 MPa) similar to the modulus of human ligaments. Biological evaluation showed that cells proliferated on the composite scaffolds and they spontaneously orientated along the direction of microfiber alignment. The microfiber architecture also induced a high level of extracellular matrix secretion, which was charac-terized by immunostaining. We found that cells produced collagen type I and type III, two main components found in ligaments. After 14 days of culture, collagen type III started to form a fibrous network. We fabricated a composite scaffold having the mechanical properties of the knitted structure and the morphological properties of the aligned microfibers. It is difficult to seed a highly macroporous structure with cells, however the technique we developed enabled an easy cell seeding due to presence of the microfiber layer. Therefore, these scaffolds presented attractive properties for a future use in bioreactors for ligament tissue engineering.
Journal of Biomechanical Engineering, 2011
Tissue engineering offers an interesting alternative to current anterior cruciate ligament (ACL) ... more Tissue engineering offers an interesting alternative to current anterior cruciate ligament (ACL) surgeries. Indeed, a tissue-engineered solution could ideally overcome the longterm complications due to actual ACL reconstruction by being gradually replaced by biological tissue. Key requirements concerning the ideal scaffold for ligament tissue engineering are numerous and concern its mechanical properties, biochemical nature, and morphology. This study is aimed at predicting the morphology of a novel scaffold for ligament tissue engineering, based on multilayer braided biodegradable copoly(lactic acid-co-(e-caprolactone)) (PLCL) fibers The process used to create the scaffold is briefly presented, and the degradations of the material before and after the scaffold processing are compared. The process offers varying parameters, such as the number of layers in the scaffold, the pitch length of the braid, and the fibers' diameter. The prediction of the morphology in terms of pore size distribution and pores interconnectivity as a function of these parameters is performed numerically using an original method based on a virtual scaffold. The virtual scaffold geometry and the prediction of pore size distribution are evaluated by comparison with experimental results. The presented process permits creation of a tailorable scaffold for ligament tissue engineering using basic equipment and from minimum amounts of raw material. The virtual scaffold geometry closely mimics the geometry of real scaffolds, and the prediction of the pore size distribution is found to be in good accordance with measurements on real scaffolds. The scaffold offers an interconnected network of pores the sizes of which are adjustable by playing on the process parameters and are able to match the ideal pore size reported for tissue ingrowth. The adjustability of the presented scaffold could permit its application in both classical ACL reconstructions and anatomical double-bundle reconstructions. The precise knowledge of the scaffold morphology using the virtual scaffold will be useful to interpret the activity of cells once it will be seeded into the scaffold. An interesting perspective of the present work is to perform a similar study aiming at predicting the mechanical response of the scaffold according to the same process parameters, by implanting the virtual scaffold into a finite element algorithm.
Journal of Bioactive and Compatible Polymers, 2008
Protein C-loaded nanoparticles coated with monomethoxypoly (ethylene oxide) (MPEO) were prepared ... more Protein C-loaded nanoparticles coated with monomethoxypoly (ethylene oxide) (MPEO) were prepared by double emulsion/solvent evaporation using water-soluble biocompatible copolymers of MPEO and polylactide, as surfactants of the secondary emulsion. The nanoparticle preparation was optimized to obtain the best yield of encapsulated protein C and provide the greatest retention of its biological activity. The nanoparticles were characterized in terms of size, zeta potential, and thickness of the MPEO external layer. Protein C-loaded nanoparticles were injected into the bloodstream of guinea pigs and the protein concentration in plasma is measured as a function of time. After a rapid release corresponding to 20% of the injected protein, the protein plasma concentration progressively decreased and reached a value close to zero after 5 h. Consequently, the in vivo fate of the fluorescent nanoparticles coated with or without MPEO is studied. The uncoated nanoparticles were rapidly captured by the circulating granulocytes while the coated ones were not. The histological analysis of the spleen, 1 hour after injection, showed that the MPEO-coated particles were retained in this organ, while the uncoated ones were not captured.
Journal of Applied Polymer Science, 2012
European Polymer Journal, 2005
ABSTRACT The predominant mechanism of the hydrolytic degradation of oligo(d,l-lactide)-grafted de... more ABSTRACT The predominant mechanism of the hydrolytic degradation of oligo(d,l-lactide)-grafted dextrans in phosphate buffer was followed by quantifying both released dextran and lactic acid from the copolymers. The studied amphiphilic copolymers, with well-defined structure, exhibited various oligo(d,l-lactide) weight fractions (FOLA) while having a quite high extent of free hydroxyl groups (>90%). Depending on their FOLA, oligo(d,l-lactide)-grafted dextrans were soluble either in water or in organic solvents (THF, toluene,…) and different prevailing mechanisms of hydrolytic degradation were observed. The copolymer soluble in THF, with longer oligo(d,l-lactide) grafts and higher FOLA, was found to degrade via a particular mechanism by which the greatest part of dextran was released into buffer medium during the first two weeks of degradation. During the initial stage of degradation, the hydrophilicity of dextran backbone was considered to be the main driving force for the hydrolytic cleavage of the ester linkage between backbone and grafts. Released oligo(d,l-lactide) grafts were found to be degraded via chain-end degradation or random degradation depending on their solubility in buffer medium. In case of water-soluble copolymers with shorter oligo(d,l-lactide) grafts and lower FOLA, the chain-end degradation was exclusively observed.
Colloids and Surfaces B: Biointerfaces, 2006
We have already shown that polylactide (PLA) nanoparticles covered with a hydrophilic polymeric l... more We have already shown that polylactide (PLA) nanoparticles covered with a hydrophilic polymeric layer can be prepared by simple emulsion/solvent evaporation by using amphiphilic copolymers as surfactants during the procedure. The external layer is then constituted by the hydrophilic part of the macromolecular surfactant. This kind of nanospheres is useful for the encapsulation of lipohilic molecules.
Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2013
ABSTRACT Aliphatic hydrocarbon oil-in-water nanoemulsions were prepared using mixtures of an amph... more ABSTRACT Aliphatic hydrocarbon oil-in-water nanoemulsions were prepared using mixtures of an amphiphilic nonionic polysaccharide (dextran modified by covalent attachment of hydrocarbon tails) and tetraethylene glycol dodecylether as stabilizers. Nanoemulsions stabilized by amphiphilic polysaccharide alone underwent Ostwald ripening. On the contrary, nanoemulsions prepared with certain mixtures of hydrophobically modified dextran and tetraethylene glycol dodecylether exhibited no significant variation of their average droplet diameter over a period of time that depended strongly on the nature of the dispersed oil. When changing from n-hexane to n-octane and n-dodecane, the period of complete inhibition of Ostwald ripening varied from 3 h to several months. Polymer–surfactant interactions and co-adsorption at oil/water interface were demonstrated by dynamic interfacial tension measurements and dilational surface rheology.
Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2008
ABSTRACT Polymeric surfactants were prepared from dextran, a neutral bacterial polysaccharide. Th... more ABSTRACT Polymeric surfactants were prepared from dextran, a neutral bacterial polysaccharide. Three series of dextran derivatives were studied: neutral dextran derivatives obtained by the attachment of hydrocarbon groups (C6 and phenoxy) to dextran chains, anionic dextran derivatives obtained by further modification of phenoxy-modified dextrans, polylactide grafted dextran copolymers obtained by a well-controlled three-step procedure. Submicronic emulsions (direct or inverse) with a controlled average diameter can be prepared by selecting the operating conditions and the polymeric surfactant used. Polymeric nanoparticles (either bulk polymer or covalent networks swelled by water) were prepared by free-radical miniemulsion polymerization. The surface of the nanoparticles is covered by a physically and/or covalently attached polysaccharide layer. The average size of the latex particles is correlated to that of the initial emulsion droplets provided that the steric stabilization of the initial droplets is enough. The surface coverage of the nanoparticles was investigated and related to the polymerization conditions.
Carbohydrate Polymers, 2012
HAL (Le Centre pour la Communication Scientifique Directe), Jan 16, 2014
Polymer, 2002
The silylation reaction of dextran with 1,1,1,3,3,3-hexamethyldisilazane (HMDS) in DMSO was studi... more The silylation reaction of dextran with 1,1,1,3,3,3-hexamethyldisilazane (HMDS) in DMSO was studied as the ®rst step of the synthesis of new amphiphilic polyester-grafted dextrans. According to the experimental conditions, i.e. dextran molar weight, medium temperature and reaction time, HMDS/OH ratio, addition of a catalyst and co-solvent, partially or totally silylated dextrans were recovered. The highest silylation yields were obtained with the lowest molecular weight dextrans. The increase in temperature medium and/or reaction time, the presence of catalyst or co-solvent favored the protection yield. Whatever the dextran used, complete silylation of the polysaccharide chain could be achieved by adequate selection of the experimental conditions. The thermal properties of resulting silylated polysaccharides were investigated by temperature modulated DSC. It was observed that T g values of partially silylated dextran were maintained between 120 and 140 8C, independently of the dextran molecular weight. Interestingly, DMSO proved to behave as an ef®cient plasticizer of (partially) silylated dextrans. The partially silylated dextrans were ef®ciently used as multifunctional macroinitiators for the controlled ring-opening polymerization (ROP) of lactone. The ROP was then promoted from the remaining hydroxyl groups in the presence of tin or aluminium activator. After polymerization and ultimate deprotection of the silylated dextran backbone, amphiphilic polyester-grafted dextrans were readily recovered. q (J.-Luc Six). Fig. 1. Dextran structure. Scheme 1. Strategy of poly(1-caprolactone)-grafted dextran synthesis.
Bio-medical materials and engineering, 2010
The aim of this study is to evaluate the toxicity of nanoparticles of poly(D,L-lactic acid) (PLA)... more The aim of this study is to evaluate the toxicity of nanoparticles of poly(D,L-lactic acid) (PLA) or poly(D,L-lactic-co-glycolic acid) (PLGA) covered by chemically esterified amphiphilic hyaluronate (HA) which will be used for intra-articular injection as a drug carrier for the treatment of arthritis (RA) and/or osteoarthritis (OA). PLA and PLGA are FDA approved polymers that are already used for the preparation of nano or microparticles. HA is a natural polysaccharide already present in the articulations known to interact with the CD44 receptors of the cells (especially chondrocytes). Therefore, we can envisage that the HA covering can improve the interactions between the cells and the nanoparticles, leading to better targeting or biodistribution. The knee of healthy male rats was injected one to two times weekly, with various concentrations of nanoparticles encapsulating Dextran-FITC. The synovial membranes and the patellae were collected aseptically and histologically analyzed to...
Macromolecules, 2000
ABSTRACT The combination of bioresorbable and biodegradable hydrophilic polysaccharides with biod... more ABSTRACT The combination of bioresorbable and biodegradable hydrophilic polysaccharides with biodegradable hydrophobic polyester chains to form totally biodegradable, nonionic brushlike amphiphilic graft copolymers useful as surfactants has been investigated. In fact, a totally controlled and original three-step procedure is described which gives access to a wide range of poly(ε-caprolactone)-grafted dextran copolymer compositions. It consists of the reversible protection of the hydroxyl groups of the polysaccharide backbone by silylation, followed by the ring-opening polymerization of ε-caprolactone initiated by the free remaining hydroxyl groups of the partially silylated dextran in the presence of aluminum and tin-based catalysts. The last step relies upon the removal of silylating groups under mild acidic conditions yielding the desired amphiphilic graft copolymers.
Macromolecules, 2004
ABSTRACT A large variety of amphiphilic polylactide-grafted dextrans has been synthesized with co... more ABSTRACT A large variety of amphiphilic polylactide-grafted dextrans has been synthesized with controlled architecture through a three-step procedure: partial protection of the dextran hydroxyl groups by silylation; ring-opening polymerization of D,L-lactide initiated from remaining hydroxyl groups on partially silylated dextran; and silyl ether deprotection under very mild conditions. Throughout the synthesis, detailed characterizations of each step led to the control of copolymer architecture in terms of graft number and lengths of graft and backbone. Depending on their proportion in polylactide, these copolymers were either water-soluble or soluble in organic solvents. The potential of these amphiphilic grafted copolymers as surfactants was estimated. Their organization at air/water or dichloromethane/water interfaces was investigated by interfacial tension measurements. Self-organization in water or toluene was evaluated using fluorescence spectroscopy. Depending on its solubility, each copolymer showed noticeable surfactant properties and was able to produce either hydrophobic or hydrated microdomains in water or toluene solutions, respectively.
Journal of Polymer Science Part A: Polymer Chemistry, 2008
The four-step synthesis of amphiphilic glycopolymers associating dextran as backbone and poly(met... more The four-step synthesis of amphiphilic glycopolymers associating dextran as backbone and poly(methyl methacrylate) (PMMA) as grafts is reported, using the ''grafting from'' strategy. In the first step, the dextran OH functions were partially acetylated. The second step consisted in linking initiator groups by reaction of 2-bromoisobutyryl bromide (B i BB) with the unprotected OH functions. Third, the atom transfer radical polymerization (ATRP) of methyl methacrylate was carried out in DMSO from the resulting dextran derivative used as a macroinitiator. Finally, the cleavage of the acetate groups led to the expected glycopolymers. Careful attention was given both to the copolymer structure and the control of polymerization. PMMA grafts were analyzed by SEC-MALLS after their deliberate cleavage from the backbone to evidence a controlled polymerization. Moreover, the mildness of the final deprotection conditions was proved to ensure acetate cleavage without either degrading dextran backbone and PMMA grafts or cleaving grafts from dextran backbone.
Journal of Polymer Science Part A: Polymer Chemistry, 2011
The synthesis of amphiphilic dextran-g-poly(methyl methacrylate) glycopolymers (Dex-g-PMMA) is st... more The synthesis of amphiphilic dextran-g-poly(methyl methacrylate) glycopolymers (Dex-g-PMMA) is studied using ''grafting from'' concept and atom transfer radical polymerization. Two strategies have been examined to control the macromolecular parameters of such glycopolymers. One is involving four steps including a protection/deprotection approach and the second one only two steps. The introduction of initiators group onto a protected acetylated dextran (and directly onto dextran) was achieved resulting in protected DexAcBr (and in unprotected DexBr). These two types of polysaccharidic macroinitiators differ in term of solubility (hydrophilic DexBr vs.
Journal of Polymer Science Part A: Polymer Chemistry, 2004
The whole controlled synthesis of novel amphiphilic polylactide (PLA)grafted dextran copolymers w... more The whole controlled synthesis of novel amphiphilic polylactide (PLA)grafted dextran copolymers was achieved. The control of the architecture of such biodegradable and potentially biocompatible copolymers has required a three-step synthesis based on the "grafting from" concept. The first step consisted of the partial silylation of the dextran hydroxyl groups. This protection step was followed by the ring-opening polymerization of D,L-lactide initiated from the remaining OH functions of the partially silylated polysaccharide. The third step involved the silylether group deprotection under very mild conditions. Based on previous studies, in which the control of the first step was achieved, this study is focused on the last two steps. Experimental conditions were investigated to ensure a controlled polymerization of D,L-lactide, in terms of grafting efficiency, graft length, and transesterification limitation. After polymerization, the final step was studied in order to avoid degradation of both polysaccharide backbone and polyester grafts. The chemical stability of dextran backbone was checked throughout each step of the synthesis. PLA-grafted dextrans and PLA-grafted (silylated dextrans) were proved to adopt a core-shell conformation in various solvents. Furthermore, preliminary experiments on the potential use of these amphiphilic grafted copolymers as liquid/liquid interface stabilizers were performed.
Journal of Polymer Science Part A: Polymer Chemistry, 2013
A cholesterol-based liquid crystal monomer, diethylene glycol cholesteryl ether acrylate (DEGChol... more A cholesterol-based liquid crystal monomer, diethylene glycol cholesteryl ether acrylate (DEGCholA), has been successfully polymerized by atom transfer radical polymerization (ATRP) for the first time. Appropriate experimental conditions to control the polymerization of DEGCholA have been investigated using a model initiator (ethyl 2-bromoisobutyrate) in tetrahydrofuran (THF) or toluene at 60 C. Well-controlled ATRP of DEGCholA was obtained using N,N,N 0 ,N 0 ,N 00 -pentamethyldiethylenetriamine as ligand in THF at 60 C. These conditions were then applied to initiate the ATRP of DEGCholA from multifunctional macroinitiators based on dextran. Using a protection/ deprotection synthetic scheme, novel graft glycopolymers (Dex-g-PDEGCholA) have been synthesized. The mesomorphic properties of DEGCholA, PDEGCholA, and Dex-g-PDEGCholA have been studied by thermal polarizing optical microscopy, differential scanning calorimetry, and X-ray scattering. PDEGCholA and Dex-g-PDEGCholA show an interdigitated smectic A phase (SmA d ) between T g (30 C) and around 170 C.
Journal of Polymer Science Part A: Polymer Chemistry, 2014
ABSTRACT Poly(d,l-lactide-co-glycolide) (PLGA) copolyesters are commonly used in biomedical appli... more ABSTRACT Poly(d,l-lactide-co-glycolide) (PLGA) copolyesters are commonly used in biomedical applications. Researches were carried out on nontoxic or low-toxic catalysts that are enough efficient to provide short polymerization times, adequate microstructure chains and similar properties than the commercial PLGA materials. In this study, PLGA were synthesized by ring-opening copolymerization (ROP) using three different catalysts. Stannous octoate is the first catalyst we used, as it is very efficient, even its toxicity is still on debate. Two others low-toxic catalysts [zinc lactate and bismuth subsalicylate (BiSS)] were also evaluated. The comparison of these ROP was realized in terms of kinetics and control of the polymerization. Then, the influence of the catalyst on the PLGA microstructure chains is reported. Finally, abiotic hydrolytic degradation rate is studied. Results described in this article show that BiSS is one very attractive catalyst to produce low toxic PLGA for biomedical applications. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014
Journal of Colloid and Interface Science, 2009
Polysaccharide-covered polyester nanoparticles were prepared using the emulsion/solvent evaporati... more Polysaccharide-covered polyester nanoparticles were prepared using the emulsion/solvent evaporation process. The core of the nanoparticles was made either of PLA or of a blend of polylactide and polylactide-grafted dextran copolymer in various proportions. The surface of the nanoparticles was covered by dextran chains via the use of water-soluble polylactide-grafted dextrans as polymeric stabilizers during the emulsification step. The characteristics of the nanoparticles (size, surface coverage, thickness of superficial layer, colloidal stability) were correlated to the structural parameters (length and number of polylactide grafts) of the copolymers as well as to their surface active properties. The complete biodegradability of the nanoparticles was evaluated by considering the rate of hydrolysis of polylactide grafts in phosphate buffer and the rate of enzymatic degradation of dextran backbone by dextranase.
Journal of Biomedical Materials Research Part A, 2000
We developed a novel technique involving knitting and electrospinning to fabricate a composite sc... more We developed a novel technique involving knitting and electrospinning to fabricate a composite scaffold for ligament tissue engineering. Knitted structures were coated with poly(L-lactic-co-e-caprolactone) (PLCL) and then placed onto a rotating cylinder and a PLCL solution was electrospun onto the structure. Highly aligned 2-lm-diameter microfibers covered the space between the stitches and adhered to the knitted scaffolds. The stress-strain tensile curves exhibited an initial toe region similar to the tensile behavior of ligaments. Composite scaffolds had an elastic modulus (150 6 14 MPa) similar to the modulus of human ligaments. Biological evaluation showed that cells proliferated on the composite scaffolds and they spontaneously orientated along the direction of microfiber alignment. The microfiber architecture also induced a high level of extracellular matrix secretion, which was charac-terized by immunostaining. We found that cells produced collagen type I and type III, two main components found in ligaments. After 14 days of culture, collagen type III started to form a fibrous network. We fabricated a composite scaffold having the mechanical properties of the knitted structure and the morphological properties of the aligned microfibers. It is difficult to seed a highly macroporous structure with cells, however the technique we developed enabled an easy cell seeding due to presence of the microfiber layer. Therefore, these scaffolds presented attractive properties for a future use in bioreactors for ligament tissue engineering.
Journal of Biomechanical Engineering, 2011
Tissue engineering offers an interesting alternative to current anterior cruciate ligament (ACL) ... more Tissue engineering offers an interesting alternative to current anterior cruciate ligament (ACL) surgeries. Indeed, a tissue-engineered solution could ideally overcome the longterm complications due to actual ACL reconstruction by being gradually replaced by biological tissue. Key requirements concerning the ideal scaffold for ligament tissue engineering are numerous and concern its mechanical properties, biochemical nature, and morphology. This study is aimed at predicting the morphology of a novel scaffold for ligament tissue engineering, based on multilayer braided biodegradable copoly(lactic acid-co-(e-caprolactone)) (PLCL) fibers The process used to create the scaffold is briefly presented, and the degradations of the material before and after the scaffold processing are compared. The process offers varying parameters, such as the number of layers in the scaffold, the pitch length of the braid, and the fibers' diameter. The prediction of the morphology in terms of pore size distribution and pores interconnectivity as a function of these parameters is performed numerically using an original method based on a virtual scaffold. The virtual scaffold geometry and the prediction of pore size distribution are evaluated by comparison with experimental results. The presented process permits creation of a tailorable scaffold for ligament tissue engineering using basic equipment and from minimum amounts of raw material. The virtual scaffold geometry closely mimics the geometry of real scaffolds, and the prediction of the pore size distribution is found to be in good accordance with measurements on real scaffolds. The scaffold offers an interconnected network of pores the sizes of which are adjustable by playing on the process parameters and are able to match the ideal pore size reported for tissue ingrowth. The adjustability of the presented scaffold could permit its application in both classical ACL reconstructions and anatomical double-bundle reconstructions. The precise knowledge of the scaffold morphology using the virtual scaffold will be useful to interpret the activity of cells once it will be seeded into the scaffold. An interesting perspective of the present work is to perform a similar study aiming at predicting the mechanical response of the scaffold according to the same process parameters, by implanting the virtual scaffold into a finite element algorithm.
Journal of Bioactive and Compatible Polymers, 2008
Protein C-loaded nanoparticles coated with monomethoxypoly (ethylene oxide) (MPEO) were prepared ... more Protein C-loaded nanoparticles coated with monomethoxypoly (ethylene oxide) (MPEO) were prepared by double emulsion/solvent evaporation using water-soluble biocompatible copolymers of MPEO and polylactide, as surfactants of the secondary emulsion. The nanoparticle preparation was optimized to obtain the best yield of encapsulated protein C and provide the greatest retention of its biological activity. The nanoparticles were characterized in terms of size, zeta potential, and thickness of the MPEO external layer. Protein C-loaded nanoparticles were injected into the bloodstream of guinea pigs and the protein concentration in plasma is measured as a function of time. After a rapid release corresponding to 20% of the injected protein, the protein plasma concentration progressively decreased and reached a value close to zero after 5 h. Consequently, the in vivo fate of the fluorescent nanoparticles coated with or without MPEO is studied. The uncoated nanoparticles were rapidly captured by the circulating granulocytes while the coated ones were not. The histological analysis of the spleen, 1 hour after injection, showed that the MPEO-coated particles were retained in this organ, while the uncoated ones were not captured.
Journal of Applied Polymer Science, 2012
European Polymer Journal, 2005
ABSTRACT The predominant mechanism of the hydrolytic degradation of oligo(d,l-lactide)-grafted de... more ABSTRACT The predominant mechanism of the hydrolytic degradation of oligo(d,l-lactide)-grafted dextrans in phosphate buffer was followed by quantifying both released dextran and lactic acid from the copolymers. The studied amphiphilic copolymers, with well-defined structure, exhibited various oligo(d,l-lactide) weight fractions (FOLA) while having a quite high extent of free hydroxyl groups (>90%). Depending on their FOLA, oligo(d,l-lactide)-grafted dextrans were soluble either in water or in organic solvents (THF, toluene,…) and different prevailing mechanisms of hydrolytic degradation were observed. The copolymer soluble in THF, with longer oligo(d,l-lactide) grafts and higher FOLA, was found to degrade via a particular mechanism by which the greatest part of dextran was released into buffer medium during the first two weeks of degradation. During the initial stage of degradation, the hydrophilicity of dextran backbone was considered to be the main driving force for the hydrolytic cleavage of the ester linkage between backbone and grafts. Released oligo(d,l-lactide) grafts were found to be degraded via chain-end degradation or random degradation depending on their solubility in buffer medium. In case of water-soluble copolymers with shorter oligo(d,l-lactide) grafts and lower FOLA, the chain-end degradation was exclusively observed.
Colloids and Surfaces B: Biointerfaces, 2006
We have already shown that polylactide (PLA) nanoparticles covered with a hydrophilic polymeric l... more We have already shown that polylactide (PLA) nanoparticles covered with a hydrophilic polymeric layer can be prepared by simple emulsion/solvent evaporation by using amphiphilic copolymers as surfactants during the procedure. The external layer is then constituted by the hydrophilic part of the macromolecular surfactant. This kind of nanospheres is useful for the encapsulation of lipohilic molecules.
Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2013
ABSTRACT Aliphatic hydrocarbon oil-in-water nanoemulsions were prepared using mixtures of an amph... more ABSTRACT Aliphatic hydrocarbon oil-in-water nanoemulsions were prepared using mixtures of an amphiphilic nonionic polysaccharide (dextran modified by covalent attachment of hydrocarbon tails) and tetraethylene glycol dodecylether as stabilizers. Nanoemulsions stabilized by amphiphilic polysaccharide alone underwent Ostwald ripening. On the contrary, nanoemulsions prepared with certain mixtures of hydrophobically modified dextran and tetraethylene glycol dodecylether exhibited no significant variation of their average droplet diameter over a period of time that depended strongly on the nature of the dispersed oil. When changing from n-hexane to n-octane and n-dodecane, the period of complete inhibition of Ostwald ripening varied from 3 h to several months. Polymer–surfactant interactions and co-adsorption at oil/water interface were demonstrated by dynamic interfacial tension measurements and dilational surface rheology.
Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2008
ABSTRACT Polymeric surfactants were prepared from dextran, a neutral bacterial polysaccharide. Th... more ABSTRACT Polymeric surfactants were prepared from dextran, a neutral bacterial polysaccharide. Three series of dextran derivatives were studied: neutral dextran derivatives obtained by the attachment of hydrocarbon groups (C6 and phenoxy) to dextran chains, anionic dextran derivatives obtained by further modification of phenoxy-modified dextrans, polylactide grafted dextran copolymers obtained by a well-controlled three-step procedure. Submicronic emulsions (direct or inverse) with a controlled average diameter can be prepared by selecting the operating conditions and the polymeric surfactant used. Polymeric nanoparticles (either bulk polymer or covalent networks swelled by water) were prepared by free-radical miniemulsion polymerization. The surface of the nanoparticles is covered by a physically and/or covalently attached polysaccharide layer. The average size of the latex particles is correlated to that of the initial emulsion droplets provided that the steric stabilization of the initial droplets is enough. The surface coverage of the nanoparticles was investigated and related to the polymerization conditions.
Carbohydrate Polymers, 2012